The basal ganglia is a heterogeneous structure which possesses a complicated neuronal circuitry and relatively high concentrations of a diverse array of neurotransmitters or neuromodulators, including dopamine, 5-hydroxytryptamine, acetylcholine, Lambda-aminobutyric acid, enkephalins and substance P. Degeneration of the basal ganglia, or the administration of drugs which interfere with synaptic transmission in this structure, is associated with severe, and frequently debilitating, motor dysfunction. Altered function or disease of this brain region will result in electrophysiological and biochemical changes in the tissue, some of which represent efforts to compensate for the distrubed behavior. The overall aim of this Center is to analyze experimentally the nature and regulation of responses in the basal ganglia which occur as a result of neural activity or acute and chronic disturbances in neurotransmission in this region. The effects of nerve stimulation and substances known to interact with putative neurotransmitter receptors and/or activate or inhibit adenylate cyclase on dopamine synthesis and release, the coupling of receptors to adenylate cyclase, and the phosphorylation of proteins such as tyrosine hydroxylase and synapsin will be examined. Protein kinases and protein phosphatases in the corpus striatum will be isolated and characterized. Dopamine receptors in the striatum will be characterized with respect to ligand binding properties and the phisiological processes they mediate. The survival and functional properties of neural and chromaffin tissue transplants inserted into the cerebral ventricles or into the substance of the brain will be investigated. In vivo dopamine release and metabolism, employing in situ electrochemical detectors, will monitored in the awake animal trained to perform specific locomotor activities. The electrophysiological effects of substance P, enkephalins and analogs of these compounds on cells in the basal ganglia and their effects on neurotransmission, adenylate cyclase activity and behavior will be examined. The localization and function of synaptic glycoproteins will be investigated with the use of monoclonal antibodies. The ontogeny of neuroactive peptide specific neurons in the basal ganglia will be explored by immunocytochemical techniques and correlated with the development of functional neurotransmission. The presence and function of leukotrienes and other products of arachidonic acid metabolism in basal ganglia will be explored. Studies on patterns of evoked potential rsponses in schizophrenics and the susceptibility of patients on chronic neuroleptic therapy to tardive dyskinesias will be conducted and correlated with levels of plasma catecholamine and catecholamine metabolites in these patiens.